The seronegative spondyloarthropathies are a group of inflammatory diseases in which the spine, peripheral joints, skin, eyes, and other tissues of the body may be involved. There are many common clinical, radiological and pathological features. The observation of the strong association of HLA-B27 antigen (60-90% compared to 8% in the normal population) has further strengthened the commonality among these diseases. The development of Reiter's syndrome and reactive arthritis in B27 positive individuals occurs after gastrointestinal infection with one of several species of bacteria, including Yersinia, Salmonella, Shigella, Campylobacter, and Chlamydia. In addition, the work from several laboratories suggest that Klebsiella pneumoniae may play a role in the pathogenesis of ankylosing spondylitis in B27 positive individuals. The mechanisms by which intestinal microbes react with B27 to induce arthritic disease is not known, however, several theories have been postulated. For instance, there may be crossreactivity between HLA-B27 gene have already been developed in our laboratory for this purpose. With these mice, we would like to 1) induce arthritic disease by immunization with intestinal bacteria; and 2) determine which aspect of the interaction between HLA-B27 and bacterial infection is responsible for inducing reactive arthritis. In addition, background and major histocompatibility genes in mice can be easily manipulated so that we can determine whether another gene in linkage disequilibrium with HLA-B27 is necessary for the production of arthritic disease. Determination of the components responsible for the promotion of disease will open several doors to immune intervention and immunotherapy.